This proposal addresses the need for a simple, sensitive screening test for the early detection and differentiation of mycobacterium species in sputum specimens. The proposed diagnostic will combine gene probes specific to mycobacterial ribosomal RNA (16S rRNA) with a proprietary integrated optic interferometer. Hybridization of rRNA to an oligonucleotide probe attached to the interferometer surface results in a refractive index change that can be quantified by the interferometer. Identification of mycobacterium species is achieved by using short gene probes of specific complementary sequences. An optical sensor based on this approach has several key advantages: 1) it allows the simultaneous determination of multiple nucleic acid targets, 2) it is sensitive (potentially <<10(4) cells/mL), 3) it is rapid (60 minute assay), 4) it is simple (no wash steps or subjective interpretation), and 5) it is low cost (<$5 per test, no expensive analytic instrumentation). In particular, the proposed approach should eliminate the need for either time-consuming bacterial culture procedures or complex target amplification methods such as PCR. PROPOSED COMMERCIAL APPLICATIONS: Mycobacterium infections, and tuberculosis in particular, are a major cause of infectious disease-related death on a worldwide scale. The tuberculosis market in the US alone is $75 to $100 million. Conventional methods for identification of the causative organism are slow, and lead to high treatment costs and patient suffering. The proposed optical sensor would enable early diagnosis through increased sensitivity combined with simultaneous multispecies identification.